An Open-Label Study to Evaluate the Efficacy and Tolerability of Xanomeline/Trospium In First Episode/Early Phase Schizophrenia Patients

Launched by VANGUARD RESEARCH GROUP · Apr 4, 2025

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment combining two medications, xanomeline and trospium, for people aged 18 to 40 who have recently been diagnosed with schizophrenia. The aim is to see how effective and tolerable this treatment is compared to their current antipsychotic medications. Participants will be monitored for 24 weeks and will complete a series of assessments, including surveys about how satisfied they are with their treatment. To qualify for the study, candidates must have had unsatisfactory results from their current medication, either because it isn't working well or they are experiencing undesirable side effects.

If you or someone you know is considering participation, it's important to know that participants must be stable on their current antipsychotic medication for at least eight weeks and should not have any other serious mental health issues or medical conditions that could affect their safety in the trial. This study is not yet recruiting, but it’s a valuable opportunity for those looking for new treatment options in managing their schizophrenia symptoms. Participants will work with mental health professionals throughout the study and will have the chance to share their experiences with the new treatment.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Participant is aged 18-40 years, inclusive, at time of signing the ICF
• • 2. Participant has a primary diagnosis of schizophrenia established by a comprehensive psychiatric evaluation based on the DSM-5 (American Psychiatric Association 2013) criteria and confirmed by Mini International Neuropsychiatric Interview for Schizophrenia and Psychotic Disorder Studies (MINI) version 7.0.2.
• • 3. Participant Scores MSQ ≤3 for the Medication Satisfaction Questionnaire (MSQ)
• • 4. Within 5 years of first antipsychotic treatment for psychosis at time of signing ICF
• • 5. Clinical reason to seek a change in antipsychotic treatment due to psychosis symptom severity, it is clinically appropriate for the participant to seek a change in antipsychotic treatment due to psychosis symptom severity, adverse effects, both, or overall patient judgement/choice.
• 6. Symptom Severity Criteria:
• • 1. Clinical reasons include Positive and Negative Syndrome Scale (PANSS) total score of ≤ 120 at screening if participant is experiencing inefficacy from current antipsychotic treatment and
• • 2. A score of ≥ 4 (moderate or greater) for ≥ 1 of the following PANSS Positive Subscale (P) items: i. Item 1 (P1; delusions), ii. Item 2 (P2; conceptual disorganization), iii. Item 3 (P3; hallucinatory behavior), iv. Item 6 (P6; suspiciousness/persecution) and
• • 3. A Clinical Global Impressions-Severity scale (CGI-S) score of ≥ 4 at screening and baseline visits.
• • OR
• 7. Adverse Event or Overall Patient Choice Criteria:
• • 1. A score of \<4 for all the following PANSS Positive Subscale (P) items: i. Item 1 (P1; delusions), ii. Item 2 (P2; conceptual disorganization), iii. Item 3 (P3; hallucinatory behavior), iv. Item 6 (P6; suspiciousness/persecution)
• • 2. Participant Scores MSQ ≤3 for the Medication Satisfaction Questionnaire (MSQ)Clinical reason to seek a change in antipsychotic treatment due to adverse effects or overall patient judgement/choice.
• • 8. Upon screening, the treatment plan is for outpatient level of care. Transition to inpatient level of care after enrollment does not exclude the patient from participating in the study
• • 9. Participant is taking an antipsychotic (AP) and the AP regimen has been stable for at least 8 weeks with at least the last 4 weeks on the same dose (i.e., untreated patients or patients receiving antipsychotic polypharmacy are excluded) prior to Screening. Participants are permitted to remain on non-prohibited (see, Exclusion Criterion, and Section 9) psychotropic medications (that are not secondary AP treatments) other than the primary pre-switch AP that have been part of their ongoing treatment regimen.
• • a. Anticholinergic drugs (e.g., benztropine) are allowed at baseline but need to be washed out during cross titration within 1 week after initiating xanomeline/trospium.
• • 10. Subject can provide informed consent. A signed informed consent form must be provided before any study assessments are performed. Subject must be fluent (oral and written) in English to consent. Female participants must be willing and capable to use birth control throughout the time of the trial as defined in Section 3.1.3
• Exclusion Criteria:
• • 1. Any DSM-5 disorder other than schizophrenia within 6 months before screening (confirmed using MINI version 7.0.2 at screening) requiring clinical attention.
• • 2. Active substance or alcohol abuse or dependence in the past 6 months (cannabis use is allowed if not fulfilling abuse criteria)
• • 3. Urine toxicology screen is positive for phencyclidine, amphetamines, opiates, cocaine, or alcohol (clinically significant alcohol use in the opinion of the Investigator)
• • 4. Developmental disorder or intellectual disability
• • 5. History of serious suicide attempt within the past 6 months
• • 6. Risk of suicidal behavior as determined by the Investigator's clinical assessment. Lifetime history of clinically significant head trauma, or current history of other acute or serious medical condition or
• • 7. History or presence of clinically significant cardiovascular (eg, untreated or unstable hypertension, clinically significant tachycardia), pulmonary, renal, hematologic, gastrointestinal (\[GI\] e.g., obstructive disorders \[including conditions that may decrease GI motility, such as ulcerative colitis, intestinal atony, and myasthenia gravis\], endocrine, immunologic, dermatologic, neurologic, or oncologic disease or any other condition that, in the opinion of the investigator, would jeopardize the safety of the participant or the validity of the study results.
• • 8. Active biliary disease (eg, symptomatic gallstones). Participants with other biliary histories are eligible and should be discussed with the medical monitor
• • 9. History or high risk of urinary retention, gastric retention,
• • 10. Untreated narrow-angle glaucoma
• • 11. An estimated glomerular filtration rate (eGFR) of \< 60 mL/min at the screening visit.
• • 12. Elevations in hepatic transaminases at screening ≥ 3× ULN for ALT and AST and/or ≥ 2× ULN for total bilirubin
• • 13. History of hypersensitivity or prior exposure to xanomeline/trospium or trospium chloride
• • 14. History of any significant drug allergy (such as anaphylaxis or hepatotoxicity).
• • 15. Intellectual disability or autism spectrum disorder (by history)
• • 16. Active substance dependence within the past 3 months (except for tobacco and cannabis)
• • 17. Participant has a history of treatment resistance to schizophrenia medications defined as failure to respond to 2 adequate courses of pharmacotherapy (a minimum of 6 weeks at an adequate dose per the label), based on TRIPP guidelines (Howes, et al 2017).
• • 18. Participant is on or has history of clozapine treatment
• • 19. Participant is on≥ 2 antipsychotics at baseline
• • 20. Participant has received a long-acting injectable antipsychotic within one injection cycle for that formulation at the time of baseline (i.e., cycles are defined by the interval in which the LAI is administered. If it is a monthly administration, then the exclusion is for one month since the last LAI administration).
• • 21. Participant is receiving other psychotropic medications other than the antipsychotic to be switched, for psychiatric and neurological drugs with Anticholinergic Risk Scale (ARS) scores \>1 (tricyclic antidepressants, paroxetine, antispasmodics, antihistamines with anticholinergic properties).
• • 22. Active biliary disease (eg, symptomatic gallstones). Participants with other biliary histories are eligible and should be discussed with the medical monitor
• • 23. Pregnancy, breastfeeding or less than 3 months postpartum or intent to get pregnant within the next 6 months
• 24. Participants with any of the following:
• • 1. history of bladder stones
• • 2. history of recurrent urinary tract infections
• 25. History of unstable hypertension or tachycardia as evidenced by:
• • 1. Blood pressure of ≥ 160/100 mmHg (seated measures) at screening
• • 2. Heart rate of ≥ 110 bpm (seated measures) at screening
• • 26. Clinically significant abnormal finding on the physical examination, medical history, or clinical laboratory results at Screening
• • 27. Current participation in another clinical trial, or participation in another clinical study in which the participant received an experimental or investigational drug agent within 3 months prior to screening